Actitudes, dudas y conocimientos de los colectivos implicados en la atención del paciente con Alzheimer: resultados de la encuesta del proyecto kNOW Alzheimer

Introducción: La enfermedad de Alzheimer (EA) involucra a colectivos diversos de profesionales y cuidadores. Las actitudes y necesidades de formación en diagnóstico temprano, tratamiento, síntomas conductuales, recursos sociosanitarios y aspectos legales o éticos son desconocidas.Métodos: Estudio observacional transversal tipo encuesta dentro del proyecto kNOW Alzheimer, iniciativa de la SEN, SEGG, SEMERGEN, SEFAC y CEAFA mediante cuestionarios específicos. Cada sociedad invitó a todos sus miembros a cumplimentarlos a través de www.knowalzheimer.com.Resultados: Participaron 114 neurólogos, 113 geriatras, 275 médicos de atención primaria, 328 farmacéuticos y 858 cuidadores. Los retrasos en el diagnóstico se originan en pacientes y cuidadores, el sistema y en los profesionales, que carecen de medios o malinterpretan síntomas tempranos. Persiste el uso del término “demencia senil”. Profesionales y cuidadores perciben buena eficacia del tratamiento. Se apuesta por el diagnóstico y tratamiento en fase pre-demencia. Hay déficit de formación en el manejo de la conducta. Los profesionales afirman que informan pero los cuidadores se sienten desinformados. Los cuidadores desean conocer cuanto antes si ellos o un familiar padecen Alzheimer. Los síntomas conductuales y la necesidad de restringir actividades son fuentes de sobrecarga. Los farmacéuticos pueden contribuir a la detección y manejo, pero precisan de formación amplia. Hay necesidad de formación en aspectos legales, bioéticos, recursos y acceso a la investigación.Conclusiones: Este proyecto ha permitido obtener información sobre actitudes y dudas de los colectivos involucrados en la atención a la EA, necesidades de formación y puntos de mejora

Development of two Spanish versions of the Verbal Selective Reminding Test

El Test de Recuerdo Verbal Selectivo (TRVS) es una de las pruebas más extensamente utilizadas para la evaluación del aprendizaje y la memoria verbales. Sin embargo, este test ha sido construido principalmente para evaluar a pacientes de habla inglesa, no existiendo todavía ninguna versión española que pueda ser utilizada para evaluar a pacientes de habla hispana. Para solventar este problema, se construyeron dos versiones españolas del Test de Recuerdo Verbal Selectivo administrándose a 48 sujetos sanos, 19-31 años, en dos sesiones separadas. Encontramos que las respuestas de los sujetos a las dos versiones fueron comparables, excepto para un índice. Todas las variables sobre ambas formas presentaron correlaciones positivas significativas. También se estudió la fiabilidad test-retest para cada orden, encontrándose que el orden 2 (en el que la forma 2 se administró primero) fue más fiable que el orden 1 (donde la forma 1 se administró primero).The Selective Reminding procedure has become a widely used test for evaluating verbal learning and memory. However, since this test was mainly devised for use in English speaking individuals, disadvantages could appear when translations of the test are applied to Spanish speaking patients. To overcome these difficulties, two Spanish versions of the Verbal Selective Reminding Test were devised and administered to 48 healthy individuals, 19-31 years in age, in two separate sessions. We found that performances on the two forms were comparable, except for one measure. All the variables on both forms yielded significant positive correlations. We also examined test-retest reliability separately for both possible orders, with Order 2 (Form 2 administered first) being more reliable than Order 1 (Form 1 administered first)

The natural frequencies of the resting human brain: an MEG-based atlas

Brain oscillations are considered to play a pivotal role in neural communication. However, detailed information regarding the typical oscillatory patterns of individual brain regions is surprisingly scarce. In this study we applied a multivariate data-driven approach to create an atlas of the natural frequencies of the resting human brain on a voxel-by-voxel basis. We analysed resting-state magnetoencephalography (MEG) data from 128 healthy adult volunteers obtained from the Open MEG Archive (OMEGA). Spectral power was computed in source space in 500 ms steps for 82 frequency bins logarithmically spaced from 1.7 to 99.5 Hz. We then applied k-means clustering to detect characteristic spectral profiles and to eventually identify the natural frequency of each voxel. Our results provided empirical confirmation of the canonical frequency bands and revealed a region-specific organisation of intrinsic oscillatory activity, following both a medial-to-lateral and a posterior-to-anterior gradient of increasing frequency. In particular, medial fronto-temporal regions were characterised by slow rhythms (delta/theta). Posterior regions presented natural frequencies in the alpha band, although with differentiated generators in the precuneus and in sensory-specific cortices (i.e., visual and auditory). Somatomotor regions were distinguished by the mu rhythm, while the lateral prefrontal cortex was characterised by oscillations in the high beta range (>20 Hz). Importantly, the brain map of natural frequencies was highly replicable in two independent subsamples of individuals. To the best of our knowledge, this is the most comprehensive atlas of ongoing oscillatory activity performed to date. Critically, the identification of natural frequencies is a fundamental step towards a better understanding of the functional architecture of the human brainThis work was supported by FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación, Spain (grant PGC2018-100682-B-I00 to AC and PC) and the Comunidad de Madrid POEJ/FSE (grant PEJD-2017-PRE/SOC-3859 to AC). MM was supported by the Universidad Autónoma de Madrid (FPI-UAM-2017 fellowship). JG was supported by Deutsche Forschungsgemeinschaft (GR 2024/5-1 and GR 2024/8-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Sex differences in the aging pattern of renin–angiotensin system serum peptidases

Background: Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. Methods: One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL). Results: Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (<55 years) men had significantly higher values of NEP serum activity than younger women. Significantly lower ACE serum activity was detected in older men compared to younger men. In women, significantly higher ACE2 serum activity was observed in older women compared to younger women. Conclusions: These results suggest a differential effect of aging on the activity of RAS enzymes in men and women, especially with respect to the breakpoint of andropausia/menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.This work was supported by a grant from the Basque Government (IT8-11/13), the University of the Basque Country UPV/EHU (UFI 11/44), and the Gangoiti-Barrera Foundation

Obesity Parameters, Physical Activity, And Physical Fitness are Correlated With Serum Dipeptidyl Peptidase IV Activity In A Healthy Population

Objective: To determine whether obesity, physical fitness, and physical activity parameters are associated with the enzymatic activity of serum dipeptidyl peptidase IV (sDPPIV) in a sample of healthy women and men. Design and methods: We have correlated parameters of obesity, physical fitness, and physical activity with sDPPIV activity in 374 healthy subjects (age: 60.7 +/- 6.9 years, body mass index: 26.1 +/- 4.1 kg/m(2)). Enzymatic activity was analyzed using spectrofluorimetry, body composition was assessed by impedanciometry, physical fitness data were obtained using the Senior Fitness Test, and physical activity data were collected by accelerometer. Pearson' s partial correlation analysis was applied to determine the relationship between DPPIV activity and the rest of parameters and significantly correlated variables were introduced into linear regression models to predict DPPIV. Results: Serum DPPIV activity was negatively associated with obesity parameters such as body mass (r = -0.112), body mass index (BMI) (r = -0.147), waist circumference (r = -0.164), waist-to-hip ratio (-0.104), and percentage of fat mass (r = -0.185). Serum DPPIV activity was positively associated with cardiovascular fitness (r = 0.138), total amount of physical activity (r = 0.153), and time spent doing light exercise (r = 0.184). Regression models revealed sex differences in enzyme activity with overall activity higher in women than in men (beta = 0.437, p < 0.001). Further, percent fat mass was an independent negative predictor of DPPIV activity (beta = -0.184, p = 0.001). Serum DPPIV activity was positively predicted based on the amount of time spent doing light physical activity (beta = 0.167, p = 0.001). Conclusion: Our results demonstrate that sDPPIV activity is positively associated with healthier parameters regarding fatness, fitness and physical activity.This work was supported by the Basque Government (GIC12/173: IT811-13) and the University of the Basque Country (UPV/EHU: PPG17/40)

Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels

Background: We investigated a sample of cognitively healthy subjects with normal Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker levels to identify the earliest variables related to longitudinal memory changes. Objective: Employing a new highly demanding learning and memory test (the Ancient Farming Equipment Test; AFE-T), we aimed to investigate whether a biomarker related to neurodegeneration (i.e., CSF tau) was associated with longitudinal memory decline. Methods: Thirty-two cognitively and biologically normal (CBN) subjects underwent MRI, neuropsychological assessment, and the AFE-T at baseline and 18 months later. To explore the relationship between cognitive performance and relevant factors, a linear model was set up. For a secondary analysis that further explore the effect of tau, the subjects were divided into CBN-Tau↓ (tau  228.64 pg/ml; n = 16). We also performed voxel-based morphometry (VBM) to identify regions of grey matter volume that would predict both baseline and longitudinal cognitive performance. Results: Our main finding was an association between CSF tau and longitudinal memory decline measured with AFE-T (B = -0.17, p < 0.05; r = -0.414; p < 0.01), and further analyses showed different evolvement between subgroups, with an accelerated decline in individuals with higher tau (F(1,31) = 8.37; p < 0.01). VBM results suggested that AFE-T performance is related to grey matter volume in a medial temporal, middle frontal, and posterior cerebellar network at baseline, and that there are strategic brain areas driving the longitudinal cognitive changes. Conclusions: The present findings provide evidence for structural and biological markers linked to cognitive aging by highlighting the role of tau, a marker of neurodegeneration, which can be related with the earliest memory changes in healthy subjects

Efectividad del plan de contingencia de la Unidad de Enfermedad Inflamatoria Intestinal ante la infección de Covid-19.

Fundamentos: La toma de decisiones en los hospitales y en sus propios servicios asistenciales apenas está referenciada en la literatura. Durante el período de pandemia por Covid-19, los servicios asistenciales han puesto en marcha planes de contingencia para minimizar las consecuencias del coronavirus en los profesionales y pacientes. Sin embargo, apenas se comparte el despliegue de esos planes de contingencia, ni sus resultados, privando de referencias para refutar, comparar o emular los citados planes a otros servicios asistenciales u hospitales. El objetivo del trabajo fue la descripción de la puesta en marcha de dichos planes ante la pandemia de Covid-19 en la Unidad de Enfermedad Inflamatoria Intestinal de un Servicio de Digestivo en el Área Sanitaria de Pontevedra e O Salnés (Galicia). Métodos: Un equipo de directivos y profesionales adaptaron al entorno sanitario las 10 medidas recomendadas por Deloitte para afrontar una pandemia. A continuación, se formularon las medidas como listado de comprobación. A partir del ciclo de mejora Plan-Do-Check-Act, se agruparon las 10 medidas en las siguientes categorías: gestión del riesgo, gestión organizacional y toma de decisiones. Por último, un equipo externo realizó una evaluación cualitativa de la puesta en marcha del plan de contingencia realizado. Resultados: La Unidad de Enfermedad Inflamatoria Intestinal del Servicio de Digestivo realizó un plan de contingencia que presenta un cumplimiento de las 10 medidas recomendadas para hacer frente a la pandemia de Covid-19 con garantías. Conclusiones: Compartir el despliegue del plan de contingencia y sus resultados es útil para identificar buenas prácticas. Este trabajo ofrece un método para evaluar las tomas de decisiones en los plantes de contingencia en situaciones de pandemia. Los resultados sitúan a la Unidad de Enfermedad Inflamatoria Intestinal en el rango de la excelencia

Cerebrospinal Fluid 7-Ketocholesterol Level is Associated with Amyloid-β42 and White Matter Microstructure in Cognitively Healthy Adults

Background:Abnormal cholesterol metabolism changes the neuronal membrane and may promote amyloidogenesis. Oxysterols in cerebrospinal fluid (CSF) are related to Alzheimer’s disease (AD) biomarkers in mild cognitive impairment and dementia. Cholesterol turnover is important for axonal and white matter (WM) microstructure maintenance. Objective:We aim to demonstrate that the association of oxysterols, AD biomarkers, and WM microstructure occurs early in asymptomatic individuals. Methods:We studied the association of inter-individual variability of CSF 24-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-OHC), amyloid-β42 (Aβ42), total-tau (t-tau), phosphorylated-tau (p-tau), neurofilament (NfL), and WM microstructure using diffusion tensor imaging, generalized linear models and moderation/mediation analyses in 153 healthy adults. Results:Higher 7-KC levels were related to lower Aβ42, indicative of greater AD pathology (p = 0.041) . Higher 7-KC levels were related to lower fractional anisotropy (FA) and higher mean (MD), axial (AxD), and radial (RD) diffusivity. 7-KC modulated the association between AxD and NfL in the corpus callosum splenium (B = 39.39, p = 0.017), genu (B = 68.64, p = 0.000), and fornix (B = 10.97, p = 0.000). Lower Aβ42 levels were associated to lower FA and higher MD, AxD, and RD in the fornix, corpus callosum, inferior longitudinal fasciculus, and hippocampus. The association between AxD and Aβ42 was moderated by 7K-C (p = 0.048). Conclusion:This study adds clinical evidence to support the role of 7K-C on axonal integrity and the involvement of cholesterol metabolism in the Aβ42 generation process

Changes in synaptic proteins precede neurodegeneration markers in preclinical Alzheimer's disease cerebrospinal fluid

Altres ajuts: Additional funding came from the "Programa 1 Enfermedad de Alzheimer y otras demencias degenerativas" from the Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), the "Fundació Bancaria La Caixa" (4560/6393) and "La Marató" organized by the television channel, TV3 (201426 10).A biomarker of synapse loss, an early event in Alzheimer's disease (AD) pathophysiology that precedes neuronal death and symptom onset, would be a much-needed prognostic biomarker. With direct access to the brain interstitial fluid, the cerebrospinal fluid (CSF) is a potential source of synapse-derived proteins. In this study, we aimed to identify and validate novel CSF biomarkers of synapse loss in AD. Discovery: Combining shotgun proteomics of the CSF with an exhaustive search of the literature and public databases, we identified 251 synaptic proteins, from which we selected 22 for further study. Verification: Twelve proteins were discarded because of poor detection by Selected Reaction Monitoring (SRM). We confirmed the specific expression of 9 of the remaining proteins (Calsyntenin-1, GluR2, GluR4, Neurexin-2A, Neurexin-3A, Neuroligin-2, Syntaxin-1B, Thy-1, Vamp-2) at the human synapse using Array Tomography microscopy and biochemical fractionation methods. Exploration: Using SRM, we monitored these 9 synaptic proteins (20 peptides) in a cohort of CSF from cognitively normal controls and subjects in the pre-clinical and clinical AD stages (n 80). Compared with controls, peptides from 8 proteins were elevated 1.3 to 1.6-fold (p < 0.04) in prodromal AD patients. Validation: Elevated levels of a GluR4 peptide at the prodromal stage were replicated (1.3-fold, p 0.04) in an independent cohort (n 60). Moreover, 7 proteins were reduced at preclinical stage 1 (0.6 to 0.8-fold, p < 0.04), a finding that was replicated (0.7 to 0.8-fold, p < 0.05) for 6 proteins in a third cohort (n 38). In a cross-cohort meta-analysis, 6 synaptic proteins (Calsyn-tenin-1, GluR4, Neurexin-2A, Neurexin-3A, Syntaxin-1B and Thy-1) were reduced 0.8-fold (p < 0.05) in preclinical AD, changes that precede clinical symptoms and CSF markers of neurodegeneration. Therefore, these proteins could have clinical value for assessing disease progression, especially in preclinical stages of AD

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis